Trypanosomiasis Lecture Notes PDF

# B.Sc. (NURSING) ## LECTURE: TRYPANOSOMIASIS ### Prof. D. Odongo #### TUESDAY 10th DECEMBER 2024 #### 9:00 am - 11:30 am # TRYPANOSOMIASIS - Trypanosomes first described in frogs 1855 - Griffith Evans identified *T. evansi* as agent of surra (a horse and camel disease) in 1880 - David Bruce ident...

# B.Sc. (NURSING) ## LECTURE: TRYPANOSOMIASIS ### Prof. D. Odongo #### TUESDAY 10th DECEMBER 2024 #### 9:00 am - 11:30 am # TRYPANOSOMIASIS - Trypanosomes first described in frogs 1855 - Griffith Evans identified *T. evansi* as agent of surra (a horse and camel disease) in 1880 - David Bruce identified *T. brucei* as cause of Nagana and demonstrated transmission by Tsetse # TRYPANOSOMIASIS - **Trypanosomiasis** - **West African Trypanosomiasis** - *T. brucei gambiense* - **Sleeping sickness** - Transmitted by Glossina (Tsetse fly) - **East African Trypanosomiasis** - *T. brucei rhodesiense* - **Sleeping sickness** - Transmitted by Glossina (Tsetse fly) - **American Trypanosomiasis** - *T. cruzi* - **Chagas' disease** - Transmitted by Triatoma # Human African Trypanosomiasis - Sleeping sickness; illness is endemic to sub-Saharan Africa. - Caused by *Trypanosoma brucei*, - Extracellular flagellated protozoan parasite - Two morphologically identical subspecies and - Transmitted to human hosts by bites of infected tsetse flies, which are found only in Africa - *Trypanosoma brucei rhodesiense* (East African or Rhodesian African trypanosomiasis) - *Trypanosoma brucei gambiense* (West African or Gambian African trypanosomiasis) # Geographical Distribution of African Trypanosomiasis - ***G. palpalis*** - In 24 countries in west and central Africa - Accounts for 98% of reported cases of sleeping sickness and causes a chronic infection - Transmitted by *Glossina palpalis* - Can not live in lab animals - Goats, cattle and pigs are reservoirs - ***G. morsitans*** - 13 countries in eastern and southern Africa - Represents under 2% of reported cases and causes an acute infection - Transmitted by *Glossina morsitans* - Can live in lab animals - Wild animals and humans are reservoirs - The major epidemiological factor in HAT is contact between humans and tsetse flies, influenced by an increasing tsetse fly density, changing feeding habits, and expanding human development into tsetse fly-infested areas # MORPHOLOGY OF TRYPANOSOMES - **Different forms:** - **Trypomastigote:** in Blood/Lymph/tissue space of various organs & Central Nervous System. Spindle shaped, central nucleus, free flagellum undulating membrane. - **Epimastigote:** in salivary gland of vector & Culture media. - **Amastigotes:** Intracellular stages # Morphological forms of trypanosomes - **Trypomastigotes** - kinetoplast is anterior - **Epimastigote** - kinetoplast is central - **Amastigote** - kinetoplast is central. Amastigotes are intracellular circular with no flagellum # Life cycle of *Trypanosoma brucei gambiense* & *T.b. rhodesiense* - During a blood meal on the mammalian host, an infected tsetse fly injects **MT** into skin tissue - Parasites enter the lymphatic system and pass into the bloodstream and transform into bloodstream trypomastigotes - Trypomastigotes are carried to other sites throughout the body, reach other body fluids - Tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host - Parasites transform into procyclic trypomastigotes in the fly's midgut, multiply by binary fission, leave the midgut, and transform into epimastigotes - Epimastigotes reach the fly's salivary glands and transform into **MT** # Mechanism of disease transmission - Mostly transmitted through the bite of an infected tsetse fly but there are other ways in which people are infected: - **Mother-to-child infection:** the trypanosome can cross the placenta and infect the fetus. - **Mechanical transmission** through other blood-sucking insects is possible, however, it is difficult to assess its epidemiological impact. - **Accidental infections:** in laboratories due to pricks with contaminated needles. - **Transmission of the parasite through sexual contact** has been reported. # Sleeping Sickness in man - Infection occurs in two stages, an initial **haemo-lymphatic stage** followed by a **meningoencephalitic stage** after the trypanosomes invade the Central Nervous System # Clinical Picture of Haemo-lymphatic stage - Incubation period (2 wks), trypanosomes multiply in subcutaneous tissues, blood and lymph - Painful skin chancre results from a characteristic local inflammation the trypansomal chancre (5-15 days after the bite), resolves spontaneously (< *gambiense*) - Intermittent fever (refractory to antimalarials), general malaise, myalgia, arthralgias, and headache; usually 3 weeks after the bite - Generalized or regional lymphadenopathy - Posterior cervical lymphadenopathy (Winterbottom sign) is characteristic of *gambiense* - Invasion of bone marrow (hypoplastic anaemia) - Facial edema (minority of patients) - Transient urticarial, erythematous, or macular rashes 6-8 weeks after onset - Trypanids (ill-defined, centrally pale, evanescent, annular, or blotchy edematous erythematous macules on the trunk) - Mild symptoms in *gambiense* but can be severe in *rhodesiense* with often fatal outcome # Clinical Picture of Neurological / Mengino-encephalitic stage - Progression: 300-500 days for *T.b. gambiense*, 21-60 days for *T.b. rhodesiense* infection. - Persistent headaches (refractory to analgesics) - Loss of appetite, wasting syndrome, and weight loss - Seizures in children (rarely in adults) - Daytime somnolence followed by nighttime insomnia - Mental, sensory, motor and neurological S&S - Progressive meningo-encephalitis with progressive neurological involvement severe dementia with sometimes aggressive behavior - Behavioral changes, mood swings, and, depression, confusion, sensory disturbances and poor coordination. - Disturbance of sleep cycle (sleeping sickness), coma which ultimately ends in death - Endocrine abnormalities: adrenal insufficiency, thyroid dysfunction and hypogonadism; and cardiac involvement, such as myocarditis, is more severe in *rhodesiense* - Disease progression and CNS invasion: 1-2 yr for *gambiense*/ 1 mo for *rhodesiense*) # Physical finding - **Early or hemolymphatic stage** - Indurated chancre at bite site - Skin lesions (trypanids) in light-skinned patients - Lymphadenopathy - Axillary and inguinal lymphadenopathy (*rhodesiense*) and cervical lymphadenopathy (*gambiense*) the classic Winterbottom sign - Fevers, tachycardia, irregular rash, edema, and weight loss - Organomegaly, particularly splenomegaly (*gambiense*) - **Late or neurologic stage** - Kerandel sign (delayed pain on compression of soft tissue) - Behavioural changes consistent with mania or psychosis, speech disorders, and seizures - Stupor and coma - Psychosis - Sensory disorders - **Complications** - Anaemia and fatigue - Wasting syndrome - Aspiration pneumonia - Meningoencephalitis and seizures - Stupor or coma (sleeping sickness) - Death - Perinatal death or abortion (after congenital infection # 3 Steps of Disease management - Disease management is made in 3 steps: - **Screen for potential infection:** Use serological tests (only available for *T.b. gambiense*) and check for clinical signs - especially swollen cervical lymph nodes. - **Diagnose and establish whether the parasite is present in body fluids.** - **Staging to determine the state of disease progression:** Entails clinical examination and analysis of the cerebrospinal fluid obtained by lumbar puncture. - Diagnosis must be made as early as possible to avoid progressing to the neurological stage in order to elude complicated and risky treatment procedures # Diagnostic considerations - In hemo-lymphatic stage DDx of recurrent fever include malaria, HIV infection, borreliosis, brucellosis, typhoid fever, and other enteric fevers. - DDx of lymphadenopathy include TB, lymphadenitis, HIV infection, and cancer. - In neurologic DDx of mental status changes include TB, meningitis, and HIV-related opportunistic infections, including cryptococcal meningitis # General Blood Studies and Serology - Anemia, hypergammaglobulinemia, low complement levels, elevated ESR, thrombocytopenia, and hypoalbuminemia - Standard serologic assay for diagnosing West African trypanosomiasis is the card agglutination test for trypanosomiasis (CATT) - Antigen detection tests based on ELISA - Culture of CSF, blood, bone marrow aspirate, or tissue specimens can be performed in liquid N.N.N OR Weinmann's media - Antibody detection in CSF and intrathecal space, PCR, and serum proteomic tests. - Isoenzyme and RFLP analysis for definitive sub-species identification. # Diagnosis of Human African Trypanosomiasis - **Laboratory Diagnosis (Smears)** - Wet smear of unstained blood or a Giemsa-stained thick smear for motile trypanosomes - Hematocrit centrifugation technique. Examine BC smears; miniature anion-exchange centrifugation technique (mAECT) - Chancre aspirate can be used as a wet preparation - Lymph node or bone marrow aspirates - Animal inoculation - **Lumber puncture & examination of CSF** - Detect trypanosomes and measure WBC counts, protein, and IgM in patients with parasitemia or positive serologies or symptoms. - Presence of Mott cells (large eosinophilic plasma cells containing IgM that have failed to secrete their antibodies. - **Diagnostic imaging** - CT Scan and MRI of the head reveal cerebral edema and white matter enhancement, respectively, in patients with late-stage African trypanosomiasis. - In cases of neurologic involvement, electroencephalography (EEG) usually shows slow wave oscillations (delta waves), a nonspecific finding. # Antigenic variation in Trypanosomes - Trypanosomes can evade the immune system - Posses genes that code for about 1000 variant forms of their surface glycoproteins (SVG). - Switch to a different variant produces a new generation not susceptible to attack by immune factors specific to the previous generation. - Increased total IgM level in serum due to antigenic variation of the surface coat of the parasite. # Treatment of Human African Trypanosomiasis - Treatment varies depending on the stage of the disease. - **Drugs used in the treatment of first Stage** - **Pentamidine:** treatment of the *gambiense* infection. General well tolerated by patients despite non-negligible undesirable effects, - **Suramin:** treatment *rhodesiense* infection. Provokes undesirable effects, including urinary tract and allergic reactions. - **Drugs used in the treatment of second stage:** - **Melarsoprol:** arsenic based, undesirable side effects, most dramatic of which is reactive encephalopathy which can be fatal (3% to 10%) - **Eflornithine:** much less toxic than melarsoprol and regimen is complex and cumbersome to apply - **Nifurtimox:** Nifurtimox-eflornithine combination therapy (NECT), introduced in 2009. Simplifies the use of eflornithine by reducing the duration of treatment and the number of IV perfusions, but not studied for *T.b. rhodesiense*. - **Drugs used in the treatment of both stages** - **Fexinidazole:** new oral treatment for *T.b.g* infection. Included in 2019 in the WHO Essential medicines list and WHO HAT treatment guidelines. - Administer within 30 min after a solid meal and under supervision of trained medical staff.. # Prevention and Control - Avoid travel to areas heavily infested with tsetse flies - Inspect vehicles before entering. - Tsetse flies are attracted to moving vehicles and dark contrasting colors - Wear wrist- and ankle-length clothing that is made of medium-weight fabric in neutral colors. - Treat asymptomatic carriers, infection can be detected by means CATT or lymph node aspiration and confirmed with smears. - Consult an infectious disease specialist for evaluation of both early- and late-stage HAT in a symptomatic patient - **Long-Term Monitoring** - In both early- and late-stage trypanosomiasis, symptoms resolve after treatment, and parasitemia clears on repeat blood smears. - Patients who have recovered from late-stage *rhodesiense* infection should undergo lumbar punctures every 3mo for the first year (every 6mo for 2 years for *gambiense*) - Reduce the reservoir of infection - Vector control using multisectoral approach. # Tsetse Trap - Tsetse fly traps are used to kill the flies. - The trap looks enough like a cow to trick the Tsetse fly - Lured by the smell of cow's urine contained in the bottle, they fly towards the blue cloth on either side of the trap. - The black cloth in the middle invites the flies to settle. They then fall into the trap and die - This trap has lowered the amount of tsetse flies in Africa. # American Trypanosomiasis - **(Chagas Disease)** # American Trypanosomiasis - Causative agent *T. cruzi* - Leading cause of cardiac disease in S. and Central America - Infection is most commonly spread through contact with the poop of an infected triatomine bug - Triatomine bug thrives in poor housing conditions (mud walls, thatched roofs), and in countries where the bug is present, people living in rural areas are at greatest risk for getting infected. # *Trypanosoma cruzi* causing Chagas' disease - Prominent kinetoplast - Trypanosoma cruzi C-shaped - Winged bug Kissing bug Triatoma or Rhodnius # Morphology of *Trypanosoma cruzi* - **Trypomastigote (Monomorphic)** - Slender shaped - Central nucleus - C or U-shaped-Free flagellum 1/3 body- Large bulging peripheral kinetoplast - **Amastigote** - Obligatory intracellular - mainly in cardiac & Skeletal muscles - Brain meninges - Nerve ganglia - cells of GIT .... etc - **Epimastigote (Vector only)** - Spindle shape- Kinetoplast anterior to central nucleus- Undulating membrane is short-terminal free flagellum # Life Cycle of *T. cruzi* - Infested triatomine bug takes a blood meal and releases trypomastigotes in its feces near the site of the bite wound. - Trypomastigotes enter the host through the wound or mucosal membranes, invade cells near the site of inoculation and differentiate into amastigotes - Amastigotes multiply by binary fission and differentiate into trypomastigotes, and then are released into the circulation as bloodstream trypomastigotes - Trypomastigotes infect cells from a variety of tissues and transform into amastigotes in new infection sites. Bloodstream trypomastigotes do not replicate - Bug becomes infected by feeding on human or animal blood containing circulating parasites. - Ingested trypomastigotes transform into epimastigotes in the vector's midgut. - Parasites multiply and differentiate in the MG and differentiate into infective metacyclic trypomastigotes in the HG # Clinical Picture of Chagas Disease - **Acute stage (1-4 mo duration)** - Active infection (circulating trypomastigotes) - Early phase typically asymptomatic (children most likely to be symptomatic), only about one-third of patients have symptoms of acute Chagas disease - Incubation period for Chagas disease is 7-14 d - First symptom is a bug bite by a reduviid or triatomine insect, typically on or near the face - After 1-3 weeks, the organism proliferates, producing a red nodule known as a chagoma, which develops a the site of the original inoculation. - Chagoma is usually located on the face or arms and can be painful. The surrounding skin becomes indurated and, later, hypopigmented - Unilateral periorbital edema of the eyelids, (Romaña sign), if bite occurs near the eye. - Infected patient may develop a flulike illness. Symptoms include a high temperature, chills, headache, irritability, tiredness, anorexia, malaise, myalgias, lymphadenopathy, and splenomegaly. - Cardiac symptoms observed in almost all patients, shortly after proliferation of the parasite begins resulting in death or progression to the chronic form # Diagnosis of Chagas Disease - **Presumptive Diagnosis** - Epidemiological history of possible exposure - living in infested house - Bug bite, chagoma, Romaña's sign - Chancre aspirate can be used as a wet preparation - Cardiac or gastro-intestinal symptoms - **Laboratory Diagnosis** - CBC count - leukocytosis with relative lymphocytosis, elevated transaminase levels in acute phase - Lymph node, liver or spleen biopsy- amastigotes - Giemsa stained or direct wet-mount blood/biopsy smears preparations - Blood cultures have positive results in patients with acute-phase illness - Xenodiagnosis - best method for diagnosis in latent or chronic phases - Serologic tests - include CFT (Machado-Guerreiro test), IFAT and ELISA. - PCR - Cruzin test (I.D.) - **Diagnostic imaging studies** - In patients with cardiac involvement, chest radiography may reveal cardiac enlargement with clear lung fields - Electrocardiography (ECG) - useful to assess for evidence of acute chagasic myocarditis or chronic Chagas cardiomyopathy. - Cardiac MRI to detect myocardial fibrosis - In colonic involvement, barium enema examination is the cornerstone for Dx (sigmoid colon is frequently dilated and elongated in nearly all cases; rectum is dilated in 80% of cases) - **Other Tests** - Lumbar puncture to assess for CNS involvement. - Cerebral spinal fluid may show pleocytosis with a predominance of lymphocytes and elevated protein level, and presence of *T. cruzi* - Histologic Findings lesion at the parasite's portal of entry - Diffuse inflammation and focal necrosis of the myocardium, as well as dense foci of fibrosis # Treatment and Management of Chagas Disease - **Medical Care** - Acute phase of Chagas disease is treated with nifurtimox or benznidazole (act on blood stream trypomastigotes and suppress parasitemia) - Management of chronic Chagas disease is supportive (bed rest, hydration, antipyretics) - Patients with bradydysrhythmias and atrial fibrillation with a slow ventricular response may require a permanent pacemaker, if they are symptomatic - Embolism or evidence of thrombosis may necessitate anticoagulant therapy - Patients, symptomatic megaesophagus can benefit from pneumatic dilation of the lower esophageal sphincter. Relapse occurs in as many as 26% of patients - Early stages of colonic dysfunction - employ a high-fiber diet and increased fluid intake, as well as laxatives. - Treat fecaloma with multiple mineral oil or saline enemas and colonic lavages - **Surgical care** - Reserved for disease that fails to respond to repeated dilatation and the most severe cases with dolichomegaesophagus - Laparoscopic transhiatal subtotal esophagectomy has been successful - Resection of the sigmoid colon as well as a portion of the rectum in patients with megacolon in whom conservative methods fail, as well as those with frequent fecal impaction or sigmoid volvulus - **Diet** - Dietary measures are generally not effective, except for high-fiber and increased fluid intake for the treatment of mild colonic dysfunction # Prevention and Control of Chagas Disease - No vaccine for Chagas disease - Improvement of human dwellings and house cleanliness to prevent vector infestation - Personal preventive measures such as bed nets - Good hygiene practices in food preparation, transportation, storage and consumption - Separation of animal stalls from house - Health education activities resulting in behavior changes - Control of vectors by use of residual insecticides to spray houses - Screening of blood donors before blood transfusions - Early diagnosis and treatment of people with medical indication - Testing of organ, tissue or cell donors and receivers - Elimination of reservoir hosts - **WHO Response** - Goal of elimination of Chagas disease transmission and provide health care for infected people suffering from the disease, both in endemic and non-endemic territories: - Chagas disease one neglected tropical disease since 2005. - WHO aims to increase networking at the global level and reinforce regional and national capacities, focusing on strengthening world epidemiological surveillance, raising awareness, promoting identification of appropriate diagnostic tests and updated case management - Southern Cone (1991), Central America, Andean Pact and Amazonian Intergovernmental Initiatives, with the Pan American Health Organization Secretariat. These multinational initiatives led to substantial reductions in transmission and increased access to diagnosis and antiparasitic treatment. # Prof David Odongo to Everyone - Recommended books Clinical Parasitology A hand book for medical Practitioners by Harsha Sherry et al - Parasitology - Protozoology and Helminthology K.D Charterjee - Medical Parasitology Markell and Voge's